The present application is generally directed to the preparation of polyamino acids. In one embodiment, the polyamino acids are homopolymers and copolymers of polyglutamic acid, polyaspartic acid and other amino acids. Polyamino acids and esters of polyamino acids are known and have a wide variety of uses. For example, U.S. Pat. No. 5,258,446 discloses polyamino acid resins for use in coating artificial leather, synthetic resin sheets or plastic products. The polyamino acid resins are C1-C4 or benzyl esters of polyglutamate and polyaspartate prepared from the polymerization of the corresponding N-carboxyanhydrides. In addition, U.S. Pat. No. 4,450,150 and U.S. Pat. No. 6,630,171 disclose copolymers of polyglutamic acid and polyglutamate which are pharmaceutically acceptable matrices for drugs or other active substances wherein the copolymer controls the rate of drug release. Additionally, U.S. Pat. No. 6,515,017 discloses derivatization of taxol with polyglutamic acid, polyaspartic acid and polylysine to increase the water solubility of taxol.
Polyglutamic acid and other polyamino acids have been prepared by a variety of routes. For example, U.S. Pat. No. 4,450,150 discloses a process wherein a benzyl glutamate/ethyl glutamate copolymer is debenzylated to produce a glutamic acid/ethyl glutamate copolymer. U.S. Pat. No. 6,630,171 discloses a process wherein polyglutamic acid/ethyl glutamate copolymers are prepared by (a) synthesis of a copolymer of polyglutamate with two different blocking groups (selected from C1-C4 alkyl and benzyl) followed by selective elimination of one of the types of blocking groups; (b) synthesis of a C1-C4 or benzyl glutamate homopolymer followed by partial elimination of some of the ester groups; or (c) synthesis of polyglutamic acid followed by partial esterification. Commercially, polyglutamic acid has been prepared by reaction of the benzyl glutamic acid, N-carboxyanhydride with a polymerization initiator to produce polybenzyl glutamate which was dried until the water content was <0.3%. This reaction was followed by acidic hydrolysis with HBr, isolation of the polyglutamic acid by extraction with acetone and subsequent proton exchange which provided the sodium salt of polyglutamic acid. Following proton exchange, the product was dialyzed and lyophilized. Upon analysis, if the benzyl content was >0.2 mole %, the mixture was subjected to acidic hydrolysis with HBr again, followed by isolation of the polyglutamic acid by extraction with acetone, proton exchange which provided the sodium salt of polyglutamic acid, dialysis and lyophilization. In addition to removal of the benzyl group from the side chain, the acidic hydrolysis cleaved the amide backbone of the polymer which produces polyglutamic acid with a lower molecular weight.